Relation of bronchial and alveolar nitric oxide to exercise-induced bronchoconstriction in atopic children and adolescents

Abstract

Background and objective: Exercise challenge test is widely used in diagnostics and follow-up of childhood asthma, but the method is complex, time consuming, and expensive. In this study, we aimed to find out whether flow-independent nitric oxide (NO) parameters (bronchial NO flux [J'aw(NO)] and alveolar NO concentration [CA(NO)]) predict exercise-induced bronchoconstriction (EIB) in atopic children and adolescents with asthma-like symptoms. Also, the respective NO parameters corrected for axial backward diffusion (J'aw(NO) [TMAD] and CA(NO) [TMAD]) were calculated and included in the analysis.

Methods: Thirty patients (6-19 yr old) with confirmed atopy (positive skin prick tests or allergen-specific IgE) and asthma-like respiratory symptoms were included in the study. Before the current investigations, none of the patients had been diagnosed to have asthma and none were on inhaled corticosteroids. Exhaled NO was measured at multiple exhalation flow rates, and exercise challenge test was carried out. Bronchial NO flux and alveolar NO concentration were calculated according to the linear method with and without correction for axial backward diffusion. Sixty-six healthy school children served as controls.

Results: The patients were divided into two groups according to EIB. Patients with EIB (EIB+ group, n = 18) had enhanced bronchial NO output as compared to patients without EIB (EIB- group, n = 12); but the EIB- group did not differ from healthy controls. EIB+ group had also higher alveolar NO concentration than EIB- group and healthy controls, but EIB- group did not differ from healthy controls. When bronchial NO flux and alveolar NO concentration were corrected for axial diffusion, J'aw(NO) (TMAD) had equal difference as J'aw(NO) between the groups as expected. However, only EIB+ had higher CA(NO) (TMAD) than healthy controls, and the patient groups did not differ from each other. In patients, bronchial NO output correlated with the magnitude of exercise-induced change in PEF (r(s) = -0.388, p = 0.034), FEV(1) (r(s) = -0.395, p = 0.031), and FEF(50%) (r(s) = -0.431, p = 0.020), i.e., the higher the bronchial NO output, the larger the decrease in PEF/FEV(1) /FEF(50%) . Alveolar NO concentrations correlated with the change in FEV(1) (r(s) = -0.439, p = 0.015), FEF(50%) (r(s) = -0.454, p = 0.013), FEF(75%) (r(s) = -0.447, p = 0.017), and FVC (r(s) = -0.375, p = 0.045). For J'aw(NO) (TMAD), the correlations and p-values were equal to those of J'aw(NO) , but, interestingly, CA(NO) (TMAD) had no significant correlations with any of the exercise-induced changes in lung function.

Conclusion: The results showed that in atopic children and adolescents, increased bronchial NO output as well as J'aw(NO) (TMAD) were associated with EIB, while alveolar NO concentration (but not CA(NO) [TMAD]) correlated with the degree of obstruction in smaller airways induced by exercise challenge.